1. Field of the Invention
The present invention relates to optical scanning systems for examining material disposed on a substrate.
2. Description of the Related Art
Microarray technology has been used to analyze a large number of complex biochemical reactions and systems in parallel. Optical scanners examine microarrays using a light beam having a few micron spot size. This technology provides a massively parallel form of analysis that increases data collection per unit time, decreases the overall time required for analysis, and uses smaller sample volumes and reagent volumes. For these and other reasons, microarray technology is well suited for genomic research.
Microarrays with an extremely large number of features are manufactured by methods described in PCT Application WO 92/10092 or U.S. Pat. Nos. 5,143,854; 5,384,261; 5,405,783; 5,412,087; 5,424,186; 5,445,934; 5,744,305; 5,800,992; 6,040,138; 6,040,193 all of which are incorporated by reference. The array features usually have dimensions from about ten (10) microns to about one hundred (100) microns. Each feature can include several million DNA molecules. The synthesis area of a substrate may be about 110 mmxc3x97110 mm and may include several individual microarray chips. An optical scanner needs to scan approximately 65,536xc3x9765,536 pixels, for microarrays having feature sizes of 10 xcexcm to 12.5 xcexcm, and approximately 32,768xc3x9732,768 pixels, for microarrays having feature sizes of 20 xcexcm to 25 xcexcm. Depending on the scanner, such scans take from several hours to several days.
The above-mentioned microarrays can be scanned by various optical scanners such as confocal galvanometer scanners described in U.S. Pat. No. 5,981,956 (which is incorporated by reference) or flying objective scanners described in U.S. Pat. No. 5,459,325 or PCT Applications PCT U599/06097 or PCT U599/24049 (all of which are incorporated by reference.). However, a reliable scanner that performs scans in a smaller amount of time would be useful in the art.
There is a need for additional high-speed, high-resolution optical scanning systems constructed and arranged for examination of biological material disposed on a substrate.
The present invention is directed to scanning systems and methods for examination of biological material associated with a substrate.
Thus, one aspect of the present invention provides an optical scanner, comprising: at least a first and a second objective lens mounted on at least one scanning module, wherein each at least one scanning module comprises at least one motor, at least one scan arm and at least one of the objective lenses; an optical coupling system comprising a light source and at least a first and second detector, wherein said optical coupling system is configured to deliver light from said light source through said at least two objective lenses to a substrate and detect light from said substrate collected by said at least a first and a second objective lens, and wherein said first detector detects light from said first objective lens and said second detector detects light from said second objective lens and so on; and a translation mechanism constructed for relative movement of said substrate and said scanning module. One such embodiment of this aspect of the invention provides an optical scanner, comprising: a first and a second scanning module, wherein each of said scanning modules comprises a motor, a scan arm and an objective lens; an optical coupling system comprising a light source and a first and a second detector, wherein said optical coupling system is configured to deliver light from said light source through said first and second objective lenses to a substrate and detect light from said substrate collected by said first and second objective lenses, and wherein said first detector detects light from said first objective lens and said second detector detects light from said second objective lens; and a translation mechanism constructed for relative movement of said substrate and said scanning module.
Another aspect of the present invention provides an optical scanning method for examining biological material, comprising the steps of: providing two objective lenses mounted on at least one scanning module, wherein each of said at least one scanning module comprises at least one motor, at least one scan arm and at least one of the at least one objective lenses; generating light of a selected wavelength and coupling said generated light to said two objective lenses; displacing said at least one scanning module on a scan path over biological material disposed on regions of a substrate; irradiating said biological material by light from each objective lens; collecting light from said biological material by each objective lens; detecting by a separate detector light collected from each objective lens; and analyzing said biological material based on said light detected by said detectors.